DOCSLIB.ORG

Basic Pharmacology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Basic Pharmacology NEONATAL PHARMACOLOGY KELIANA O’MARA, PHARMD, BCPS NOVEMBER 17, 2016 OBJECTIVES • Describe medication use in neonates and mothers (pre and postnatal) • Identify characteristics of maternal drugs that may impact fetus/neonate • Define the impact of pharmacokinetics on neonatal drug exposure • Review examples of medication use in neonates where neonatal pharmacology is important DRUG THERAPY • Goal is to administer a given drug at a given dose to achieve a desired therapeutic effect while minimizing risk of toxicity Pauwels S, Allegaert K. Arch Dis Child 2016;0:1–5. MEDICATION USE IN NEONATES • Nearly all medications used in the NICU are done so off-label • Limited clinical data in neonates leads to extrapolation from more extensively studied patient populations – Clinical data from other patient populations with animal data and known developmental pharmacology of neonates to determine best guess for drug and dosing regimens • Maturation of organ systems leads to differences in dosing needs throughout spectrum of NICU stay – Up to 1-log value of variability seen intra- and interpatient weights (0.5 to 5 kg) HISTORY OF UNEXPECTED ADVERSE EFFECTS • Kernicterus (sulfonamides, ceftriaxone, ibuprofen?) • Gray baby syndrome (chloramphenicol) • Gasping syndrome (benzyl alcohol—enoxaparin, midazolam) • Apnea (promethazine) • Metabolic acidosis (propylene glycol) NEONATAL PHARMACOLOGY • Prediction of drug-specific effects and adverse effects based on pharmacokinetics and pharmacodynamics – Pharmacokinetics: concentration/time profile – Pharmacodynamics: concentration/effect profile MATERNAL DRUG EXPOSURE • More than 90% of pregnant women self-report taking at least one medication during pregnancy1 – Average number of medications: 4.2 – Half of all pregnant women take more than 4 medications 1. Koren et al. JPPT 2013 Exposure to teratogen during a specific developmental stage Normal Gamete Blastocyst Embryo Fetus Newborn sterility death death death Major structural Functional abnormalities abnormalities DRUG TRANSFER ACROSS THE PLACENTA • Most drugs ingested by pregnant women cross the placenta – Most women expose fetus to 1-8 drugs during pregnancy • Human placenta unique from other species as organ of drug transfer – Higher permeability after16 weeks gestation – Later in gestation, increases in uterine blood flowà higher passage across the placenta DRUG TRANSFER ACROSS THE PLACENTA • Most drugs cross via passive diffusion • Characteristics of highly diffused drugs: – Low molecular weight (< 600 d), non-ionized, lipid soluble • Strongly ionized compounds poorly diffuse – Exceptions: ampicillin, methicillin DRUG TRANSPORT ACROSS THE PLACENTA • Facilitated diffusion: concentration gradient, requires no energy, inhibited by competitive analogues, saturable • Occurs with drugs structurally similar to endogenous compounds – Cephalosporins, gancyclovir, and corticosterone PLACENTAL PROTECTION FOR FETUS • Placental function – Semipermeable barrier – Limited drug metabolism by placenta • Drugs enter the fetus through the umbilical vein – 40-60% of the umbilical blood flow enter into the fetal liver FDA PREGNANCY CATEGORIES Category Animal Data Human Data A No risk No risk No risk No data B Risk No risk C* Risk No data D* Harmful Harmful X Harmful Harmful *Potential benefit may outweigh potential risk to fetus FDA PROPOSED CHANGES TO LABELING • Elimination of the 5 categories – Misleading to providers and women – Risk for C, D, and X are based on risk and benefits to patient, not just risk – Categories do not distinguish differences in frequency, severity, and type of fetal toxicities • Two subsections: pregnancy and lactation – Labor and delivery section eliminated – Three components: risk summary, clinical considerations, and data section http://www.gpo.gov/fdsys/pkg/FR-2008-05-29/pdf/E8-11806.pdf BREASTFEEDING AND MEDICATION USE • Rates of breastfeeding in the US per CDC 2013 report card: – 77% infants begin life breastfeeding; 49% breastfeeding at 6 months, 27% at 12 months • ~90% of women take some form of medication during the first week postpartum – In a study of 14,000 pregnant/breastfeeding women, 79% used meds while breastfeeding, avg intake: 3.9 drugs • Maternal compliance with drug therapy can be erratic while breastfeeding secondary to infant concerns DRUG TRANSFER INTO BREAST MILK • Most drugs cross into breast milk but amount and concentration transferred are low and relatively safe for infant • Maternal and infant characteristics influence amount of drug transferred into milk MATERNAL FACTORS • Dose and duration of therapy – Low dose, infrequent dosing, short duration – If drug contraindicated, may consider “pump and dump” • Route of administration – Drugs given IV before of poor PO bioavailability are usually poorly absorbed by infant through milk • Drug pharmacokinetics – Drugs with long half-life may result in cumulative exposure in infant INFANT FACTORS • Total amount of drug exposure to infant: – Concentration in breast milk and volume of milk ingested per day • Gestational age and postnatal age determine infants ability to absorb, metabolize, and excrete drug – Preterm infant less able to metabolize and excrete drugs because of less mature liver and kidneys PHARMACOKINETICS • What the body does to the drug • Describes the movement of drug into, through, and out of the body – Absorption: translocation of drug from site of administration into blood – Distribution: space within the body that drug must fill to reach steady-state – Metabolism: biotransformation of drug to metabolites – Excretion: removal of drug from the body • Must consider both maternal and neonatal pharmacokinetic profiles to predict fetal/neonatal outcomes of medication use ASHP Chapter. http://www.ashp.org/doclibrary/bookstore/p2418-chapter1.aspx MATERNAL ABSORPTION • Increased gastric emptying time • Decreased intestinal motility • Result: delayed absorption time, delayed peak effect, negligible effect on steady-state MATERNAL DISTRIBUTION • Body composition – Increase in maternal fat relatively constant with weight gain – Result: increased doses needed for fat-soluble drugs, accumulation may occur in adipose tissue (increased half-life, prolonged drug effects) • Body volume – Increased total body water, extracellular water, and plasma volume – Increased cardiac output, heart rate, stroke volume – Result: decreased serum concentrations water-soluble drugs MATERNAL DISTRIBUTION • Serum proteins decreased • Increased free fraction of highly bound drugs • Result: increased exposure across placenta to protein-bound drugs MATERNAL METABOLISM • Increased hepatic enzyme activity • Result: increased metabolism, clearance – Higher doses needed of drug to maintain effect NEONATAL PHARMACOKINETICS • Important clinical features – Absorption – Distribution – Metabolism – Excretion NEONATAL ABSORPTION • Enteral • Percutaneous • Subcutaneous • Intramuscular • Intrapulmonary • Rectal NEONATAL ABSORPTION-ENTERAL • Most drugs absorbed in small intestine • Gastrointestinal pH, transit time, and gastric emptying play important roles in total drug exposure time and absorption • Gastric acidity – Does not reach adult levels until 2-3 years of age – Introduction of nutrition helps regulate GI function – Acid production function of postnatal age, not PCA – Length/frequency of feeding can impact pH – Drugs that are weak acids absorbed more slowly than weak bases NEONATAL ABSORPTION-ENTERAL Tayman et al. JPPT 2011 FACTORS AFFECTING GASTRIC EMPTYING • Gestational and postnatal age • Increased: – Extensively hydrolyzed formula compared to intact or partially hydrolyzed • Decreased: – Increasing caloric density and medium-chain triglycerides • Does not approach adult times until 6-8 months of life NEONATAL ABSORPTION- PERCUTANEOUS • Degree of skin hydration and relative absorption surface area – Inversely related to thickness of stratum corneum • Term infants – Intact skin barrier function – Ratio of surface area to body weight much higher than adults – 2.7 x greater amount drug exposure NEONATAL ABSORPTION- SUBCUTANEOUS • Subcutaneous injection goes into the fatty layer of tissue under the skin – Little blood flow to fatty tissue – Injected medication absorbed more slowly • Premature neonates generally lack the fatty tissue of the subcutaneous space that makes this dosing method effective NEONATAL ABSORPTION- INTRAMUSCULAR • Physicochemical and physiologic factors affect rate – Drug pH, lipophilicity – Blood flow, total surface area of muscle at injection site • Rate of absorption may be lower – Extent of absorption may be higher secondary to higher density of skeletal muscle capillaries compared to older children and adults NEONATAL ABSORPTION-OTHER Intrapulmonary • Final stages of normal lung development interrupted in premature infants – Decreased lung volumes, gas exchange, capillary surface area • Potentially altered patterns of drug disposition and absorption – Ventilatory type and settings (high-frequency vs. conventional) Rectal • Rapid, complete absorption • Dosage formulations often problematic NEONATAL DISTRIBUTION • Occurs after reaching systemic circulation • Factors affecting distribution: – Body compartment size and composition – Hemodynamics (cardiac output, regional blood flow) – Membrane permeability – Fat/water solubility of drugs – Plasma protein binding NEONATAL DISTRIBUTION-PROTEIN BINDING • Affinity of albumin for acidic drugs increases from birth to early infancy • Alpha1-acid glycoprotein binds basic drugs – Neonates have half the adult concentration
Load more

Recommended publications
  • Clinical an Urgent Care Approach to Complications and Conditions of Pregnancy Part 2
    Clinical An Urgent Care Approach to Complications and Conditions of Pregnancy Part 2 Urgent message: From pregnancy confirmation to the evaluation of bleeding, urgent care centers are often the initial location for management of obstetric-related issues. Careful use of evidence-based guidelines is the key to successful outcomes. DAVID N. JACKSON, MD, FACOG and PETAR PLANINIC, MD, FACOG Introduction rgent care providers are called upon to manage a Uvariety of complaints in pregnancy. Some conditions can be managed at the urgent care center whereas others require stabilization and transport to a center with expert obstetrical capabilities. In all situations, practitioners should consider that a gestational age of fetal viability (many centers now use 23 to 24 weeks) is best served with referral for continuous fetal monitor- ing if there is bleeding, trauma, significant hypertension, relative hypoxemia (O2 saturation less than 95% for pregnant women), or contractions. Part 2 of this two- part series will discuss: Ⅲ Bleeding in pregnancy Ⅲ Ectopic gestation Ⅲ Trauma and pregnancy Ⅲ Acute abdominal pain in pregnancy Dr. Jackson is Professor of Maternal-Fetal Medicine at the University of Nevada, School of Medicine, Las Vegas, Nevada. Dr. Planinic is Assistant Professor of Obstetrics and Gynecology at the University of Nevada, School of Medicine, Las Vegas, Nevada. © gettyimages.com www.jucm.com JUCM The Journal of Urgent Care Medicine | September 2013 9 AN URGENT CARE APPROACH TO COMPLICATIONS AND CONDITIONS OF PREGNANCY Figure 1. Bleeding endocervical polyp with Evaluation of vaginal bleeding should follow a sys- inflammation tematic process. History of last menses and sexual activ- ity determines the possibility of pregnancy.
    [Show full text]
  • USMLE – What's It
    Purpose of this handout Congratulations on making it to Year 2 of medical school! You are that much closer to having your Doctor of Medicine degree. If you want to PRACTICE medicine, however, you have to be licensed, and in order to be licensed you must first pass all four United States Medical Licensing Exams. This book is intended as a starting point in your preparation for getting past the first hurdle, Step 1. It contains study tips, suggestions, resources, and advice. Please remember, however, that no single approach to studying is right for everyone. USMLE – What is it for? In order to become a licensed physician in the United States, individuals must pass a series of examinations conducted by the National Board of Medical Examiners (NBME). These examinations are the United States Medical Licensing Examinations, or USMLE. Currently there are four separate exams which must be passed in order to be eligible for medical licensure: Step 1, usually taken after the completion of the second year of medical school; Step 2 Clinical Knowledge (CK), this is usually taken by December 31st of Year 4 Step 2 Clinical Skills (CS), this is usually be taken by December 31st of Year 4 Step 3, typically taken during the first (intern) year of post graduate training. Requirements other than passing all of the above mentioned steps for licensure in each state are set by each state’s medical licensing board. For example, each state board determines the maximum number of times that a person may take each Step exam and still remain eligible for licensure.
    [Show full text]
  • HHS Public Access Author Manuscript
    HHS Public Access Author manuscript Author Manuscript Author ManuscriptObstet Gynecol Author Manuscript. Author Author Manuscript manuscript; available in PMC 2016 January 12. Published in final edited form as: Obstet Gynecol. 2013 October ; 122(4): 885–900. doi:10.1097/AOG.0b013e3182a5fdfd. Prophylaxis and Treatment of Anthrax in Pregnant Women: A Systematic Review of Antibiotics Dana Meaney-Delman, MD MPH1, Sonja A. Rasmussen, MD MS1, Richard H. Beigi, MD2, Marianne E. Zotti, DrPH1, Yalonda Hutchings, MD MPH1, William A. Bower, MD1, Tracee A. Treadwell, DVM MPH1, and Denise J. Jamieson, MD MPH1 1Centers for Disease Control and Prevention, Atlanta, Georgia 2Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Infectious Diseases and Obstetric Specialties, Magee-Women’s Hospital of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania Abstract Objective—To review the safety and pharmacokinetics of antibiotics recommended for anthrax post-exposure prophylaxis and treatment in pregnant women. Data Sources—Articles were identified in the PUBMED database from inception through December 2012 by searching the keywords ([“pregnancy]” and [generic antibiotic name]). Additionally, hand searches of references from REPROTOX, TERIS, review articles and Briggs’ Drugs in Pregnancy and Lactation were performed. Methods of Study Selection—Articles included in the review contain primary data related to the safety and pharmacokinetics among pregnant women of five antibiotics recommended for anthrax post-exposure prophylaxis and treatment (ciprofloxacin, levofloxacin, moxifloxacin, doxycycline, amoxicillin), and of nine additional antibiotics recommended as part of the treatment regimen (penicillin, ampicillin, linezolid, clindamycin, meropenem, doripenem, rifampin, chloramphenicol, or vancomycin). Tabulation, Integration and Results—The PUBMED search identified 3850 articles for review.
    [Show full text]
  • Effect of Synbiotic on the Treatment of Jaundice in Full Term Neonates: a Randomized Clinical Trial
    Pediatr Gastroenterol Hepatol Nutr. 2019 Sep;22(5):453-459 https://doi.org/10.5223/pghn.2019.22.5.453 pISSN 2234-8646·eISSN 2234-8840 Original Article Effect of Synbiotic on the Treatment of Jaundice in Full Term Neonates: A Randomized Clinical Trial Shokoufeh Ahmadipour ,1,2 Parastoo Baharvand ,3 Parisa Rahmani ,4 Amin Hasanvand ,5 and Azam Mohsenzadeh 2 1Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran 2Department of Pediatrics, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 3Department of Social Medicine, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 4Pediatric Gastroenterology and Hepatology Research Center, Tehran University of Medical Sciences, Tehran, Iran 5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran Received: Jun 27, 2018 Revised: Mar 28, 2019 ABSTRACT Accepted: Apr 8, 2019 Purpose: Jaundice accounts for most hospital admissions in the neonatal period. Nowadays, Correspondence to in addition to phototherapy, other auxiliary methods are used to reduce jaundice and the Azam Mohsenzadeh length of hospitalization. This study aimed to investigate the effect of probiotics on the Department of Pediatrics, Faculty of Medicine, Lorestan University of Medical Sciences, treatment of hyper-bilirubinemia in full-term neonates. Anooshirvan Rezaei Square, Khorramabad, Methods: In this randomized clinical trial, 83 full-term neonates, who were admitted to the Lorestan 6813833946, Iran. hospital to receive phototherapy in the first 6 months of 2015, were randomly divided into E-mail: [email protected] two groups: synbiotic (SG, n=40) and control (CG, n=43). Both groups received phototherapy Copyright © 2019 by The Korean Society of but the SG also received 5 drops/day of synbiotics.
    [Show full text]
  • Anti-Infective Drug Development in Neonates September 15, 2016
    Anti-Infective Drug Development in Neonates September 15, 2016 Page 1 1 FOOD AND DRUG ADMINISTRATION (FDA) 2 3 PUBLIC WORKSHOP: 4 FACILITATING ANTI-INFECTIVE DRUG DEVELOPMENT FOR 5 NEONATES AND YOUNG INFANTS 6 7 September 15, 2016 8 9 10 Sheraton Silver Spring 11 8777 Georgia Avenue 12 Silver Spring, Maryland 20910 13 14 15 16 17 18 19 20 21 Reported by: Chaz Bennett 22 Capital Reporting Company www.CapitalReportingCompany.com 202-857-3376 Anti-Infective Drug Development in Neonates September 15, 2016 Page 2 1 P A R T I C I P A N T S 2 3 John Alexander, MD, MPH 4 Deputy Director 5 Division of Pediatric and Maternal Health (DPMH) 6 Office of Drug Evaluation IV (ODEIV), CDER 7 Food and Drug Administration, Silver Spring, Maryland 8 9 Gerri Baer, MD 10 Medical Officer, Office of Pediatric Therapeutics 11 Food and Drug Administration, Silver Spring, Maryland 12 13 Danny Benjamin, MD, PhD, MPH 14 Kiser-Arena Distinguished Professor of Pediatrics 15 Chair, Pediatric Trials Network 16 Faculty Associate Director, Duke Clinical 17 Research Institute 18 Duke University, Durham, North Carolina 19 20 21 22 www.CapitalReportingCompany.com 202-857-3376 Anti-Infective Drug Development in Neonates September 15, 2016 Page 3 1 P A R T I C I P A N T S 2 (Continued) 3 4 John Bradley, MD 5 Professor and Chief of the Division of Infectious 6 Diseases in the Department of Pediatrics 7 University of California, San Diego 8 9 Maria Fernandez Cortizo 10 PDCU 11 12 John Farley, MD, MPH 13 Deputy Director 14 Office of Antimicrobial Products (OAP), CDER 15 Food and Drug Administration, Silver Spring, Maryland 16 17 William Hope, PhD 18 Professor of Therapeutics and Infectious Diseases 19 University of Liverpool, Liverpool, U.K.
    [Show full text]
  • Iatrogenic Complications in the Neonatal Intensive Care Unit
    Journal of Perinatology (2010) 30, S51–S56 r 2010 Nature America, Inc. All rights reserved. 0743-8346/10 www.nature.com/jp REVIEW Iatrogenic complications in the neonatal intensive care unit KC Sekar Department of Pediatrics, Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA In neonatal medicine, significant iatrogenic events leading With the introduction of novel technologies and approaches in neonatal to severe morbidity and death have been identified and addressed. care and the lack of appropriately designed and well-executed randomized Low incubator temperature leading to death (1930); irradiation clinical trials to investigate the impact of these interventions, iatrogenic causing thyroid cancer, and excess oxygen exposure causing complications have been increasingly seen in the neonatal intensive care retinopathy of prematurity and blindness (1940); excess unit. In addition, increased awareness and the introduction of more synthetic vitamin K, sulfisoxazole and chloramphenicol causing appropriate quality control measures have resulted in higher levels of kernicterus and gray baby syndrome (1950); intrauterine suspicion about and increased recognition of complications associated with exposure to thalidomide causing limb defects (1960); umbilical delivery of care. The incidence of complications also rises with the increased arterial catheter, tolazoline and total parenteral nutrition (TPN) length of hospital stay and level of immaturity. Approximately half of the causing thrombosis, hypotension and essential fatty acid deficiency, iatrogenic complications are related to medication errors. The other respectively (1970); vitamin E and propylene glycol causing complications are due to nosocomial infections, insertion of invasive organ damage, hyperosmolarity and seizures (1980); and catheters, prolonged mechanical ventilation, administration of parenteral mechanical ventilation and systemic corticosteroid administration nutrition solution, skin damage and environmental complications.
    [Show full text]
  • Learning Objectives: 1. Relation of Drugs and Lactation 2. Factors Modifying Passage of Drugs in Milk 3
    Learning Objectives: 1. Relation of drugs and lactation 2. Factors modifying passage of drugs in milk 3. Effects of drugs on milk production 4. Role of lactation on drugs excretion This lecture was done by: 5. Drug safety during lactation / use of Abdullah Saleh Bawazir safe drugs 6. Drugs contraindicated during lactation And reviewed by: Tuqa Alkaff Lactaon: • Breast feeding is very important because breast milk is the healthiest form of milk for babies. • It provides the baby with immunoglobulins (IgA, IgM) that are essenAal for protecAon against gastroenteriAs. Drugs & Lactaon: . Most drugs administered to breast feeding woman are detectable in milk. The concentraon of drugs achieved in breast milk is usually low (< 1 %). However, even small amounts of some drugs may be of significance for the suckling child. (all the execratory mechanisms are going down in babies) Pediatric populaon are classified into: • Newborn: less than one month old – Preterm neonates: born before 38 weeks of pregnancy (it's the harmful stage) – Full-term neonates: 38-42 weeks of gestaonal age • Infants (babies): 1 month – 12 months of age • Children: 1 -12 years of age – Toddler (young child): 1-5 years – Older child: 6-12 years • Adolescent: 13-18 years 2 Pharmacokine%cs in pediatric: • Higher gastric PH • Higher concentraon of free drug • Higher percenrage of body water • Neonate’s especially premature babies have limited capacity for metabolism and excreAon. • Neonates have very limited rate of metabolism due to immaturity of liver enzymes. • Renal clearance is less efficient: ( decrease Renal blood flow – decrease GFR). • The epithelium of the breast alveolar cells is most permeable to drugs during the 1st week postpartum, so drug transfer to milk may be greater during the 1st week of an infant’s life.
    [Show full text]
  • Is Pediatric Labeling Really Necessary?
    Is Pediatric Labeling Really Necessary? Michael L. Christensen, PharmD; Richard A. Helms, PharmD; and Russell W. Chesney, MD ABBREVIATIONS. FDA, US Food and Drug Administration; For solid dosage forms, parents often must divide FDCA, Food, Drug and Cosmetic Act; GFR, glomerular filtration adult tablets in halves or quarters to get an appro- rate; BSA, body surface area. priate dose for their child. This results in imprecise dosing that can lead to poor therapeutic response. abeling refers to the label on the drug container Practitioners are left to use empiric therapy in and all printed materials, including the pack- treating their pediatric patients because of the inad- age insert, that accompanies the product. La- equate information available for prescribing of L drugs. They often must choose between not treating beling of a drug indicates that there is substantial evidence from adequate and well controlled clinical children with potentially beneficial medications be- trials for the safe and effective use of that drug. cause they are not approved for use in children, or to Labeling provides important information on clinical treat them with these medications based on adult pharmacology, indications and usage, contraindica- studies and limited or anecdotal experience in chil- tions, precautions, adverse effects, dosage, and ad- dren. In either case, children may not be prescribed ministration. Unfortunately for children, most drug optimal therapy. labeling contains the precautionary disclaimer, be- cause safety and efficacy in children have not been FOOD, DRUG AND COSMETIC ACT established. Concern for the risk to public health and safety The availability of safe and effective drugs has with unsanitary food and adulterated drugs, a com- been directly responsible for the improvement in mon problem during that time, lead to passage of health over the past 50 years.
    [Show full text]
  • Abortus, 4 Absolute Neutrophil Count, 146 Absorption
    Index A on respiratory syncytial virus, 158, 160 on sedation management, 112 Abortus, 4 on systemic corticosteroids, 88 Absolute neutrophil count, 146 on vaccinations, 187 Absorption, 17 on Vitamin K IM, 10-11 extravascular, 18 American College of Chest Physicians, 159 gastrointestinal, 18 American College of Emergency Physicians, 159 intramuscular, 18 American College of Obstetrics and Gynecology, 61 percutaneous, 19 American Congress of Obstetricians and rectal, 19 Gynecologists, 145 Academy of Breastfeeding Medicine, 49, 61 American Society for Parenteral and Enteral Acetaminophen, 21, 119, 126 Nutrition, 30, 34 PDA and, 103-104 American Society of Health-System Pharmacists vaccination response and, 191-192 (ASHP), 34 Acid ionization constant, breast milk and, 47 American Thoracic Society, 159 Acid-base balance, 32 Amino acids, 30, 34-35 Activity, 5 Aminoglycoside(s), 19, 134, 172 Acute lung injury, 84-85 Aminophylline, 69 Acyclovir, 46 Aminosyn, 30 parenteral, 147-148 Amoxicillin-sulbactam, 172 Addiction, maternal, 61 Amphotericin B, 137 Adverse drug events, methylxanthine toxicity, 71 Ampicillin, 6, 134, 172 Adverse effects, neonatal abstinence treatment, 60 Ampicillin-sulbactam, 172 Airway patency maintenance, 68 Anaerobic antibiotic therapy, 172 Albuterol, 87, 161 Analgesia Alcohol, 48 common agents for, 127-129 Alginate, 181 pharmacologic agents for, 118-119 Alpha agonists, 115-116 principles of, 116-117 Aluminum toxicity, 36-37 Analgesics, 123 American Academy of Pediatrics, 45 reversal of, 121 acyclovir shortage recommendations,
    [Show full text]
  • Evidence of Drug Safety in Pregnancy
    DRUGS IN PREGNANCY Evidence of drug safety in pregnancy For an area as complex as prescribing in pregnancy, unfortunately, there is very little information in the literature to support practice. Newer antimicrobials are trialled excluding pregnant women for reasons of risk-avoidance and, therefore, prescribers must rely on post-marketing surveillance data. For some medications, this takes the form of a formal registry (for example, the antiretroviral pregnancy registry). Obviously, prospective safety data from Phase I/II clinical trials is preferable, but in the absence of this, registry data provides some reassurance. Older antibiotics, on the other hand, may have many years of practical experience to suggest their safety, but little robust scientific evidence to support their safe use. Evidence of treatment efficacy in pregnancy Large prospective trials of treatment in pregnancy are conspicuously absent from the literature. There have been a number of Cochrane reviews on different topics in the treatment of infections in pregnancy – from asymptomatic bacteriuria to bacterial vaginosis. All of the reviews have in common very heterogeneous primary articles and cautious recommendations based on lack of data. In general, antibiotics are effective at treating the infection in question, but studies are underpowered to provide information on optimum therapy or fetal safety. 1 Done by : Pharm.D –Neda'Rwashdeh Infection and pregnancy Immune tolerance’ in pregnancy is widely discussed and there are some data to suggest that pregnant women are at slightly higher risk of developing disease from some infections (including poliomyelitis, smallpox, hepatitis A and falciparum malaria). Also, the risk of severe disease and death are increased for some infections.
    [Show full text]
  • A Pediatric Perspective on the Unique
    A Pediatric Perspective on the Unique Vulnerability and Resilience of the Embryo and the Child to Environmental Toxicants: The Importance of Rigorous Research Concerning Age and Agent Robert L. Brent, MD, PhD*; Susanne Tanski, MD‡; and Michael Weitzman, MD‡ 1 ABBREVIATIONS. PCB, polychlorinated biphenyl; MPE, maximal cal agents. In fact, the publication edited by Miller permissible exposure; NOAEL, no observable adverse effect level. was primarily devoted to exposures to the embryo and the fetus. Because the embryo and the child are growing and their tissues and organs are differenti- here is realistic concern about the impact of ating, deleterious effects may occur at lower expo- environmental influences on the health of hu- sures to some chemicals, drugs, and physical agents Tman populations. First, exposure to environ- and produce more severe effects than those seen in mental agents continues despite successes in reduc- adults. In fact, some effects may not occur in adults. ing exposures to known toxicants such as lead, Thus, maximal permissible exposures (MPEs) for polychlorinated biphenyls (PCBs) and tobacco some environmental chemicals should be lower for smoke. Second, there has been increasing concern the embryo and the child. about the cause of autism and other neurodevelop- It is important to note that children and adoles- mental problems and hypotheses that environmental cents have better recuperative capacities than adults influences may play a role in the prevalence of these for many toxic agents, and, similarly, appropriate and other such childhood and adult conditions as drug dosages may be lower or higher on a mg/kg or asthma and obesity.
    [Show full text]
  • CHLORAFAST, Eye Drops, Solution, 0.5 %W/V
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME CHLORAFAST, Eye drops, solution, 0.5 %w/v 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each mL contains 5mg of chloramphenicol equivalent to 0.5%w/v. Excipient with known effect: phenyl mercuric nitrate For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Eye drops, solution. CHLORAFAST is a colourless to faint yellow aqueous solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications For the treatment of bacterial conjunctivitis and other superficial ocular infections caused by chloramphenicol-sensitive organisms. 4.2 Dose and method of administration Adults and children (including the Elderly) Instil 1 or 2 drops in the affected eye(s) every two to six hours for two to three days. The interval between applications may then be increased. Treatment should be continued for at least 48 hours after the eye appears normal. Information for patients In order to minimise systemic absorption of CHLORAFAST eye drops, apply gentle pressure to the tear duct for approximately one minute immediately after application. Care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Do not touch dropper tip to any surface, as this may contaminate the solution. 4.3 Contraindications CHLORAFAST is contraindicated in individuals with a history of hypersensitivity to any excipients and/or toxic reaction to the medicine (refer section 6.1). 4.4 Special warnings and precautions for use Bone marrow hypoplasia, including aplastic anaemia and death, has been rarely reported following local application of chloramphenicol. Chloramphenicol should not be used when less potentially dangerous agents would be expected to provide effective treatment.
    [Show full text]